ROME — Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin. The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28–30 days follow-up, similar to those of the enoxaparin/warfarin-treated controls. And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is not possible with warfarin,” Andreas Goette, MD, said at the annual congress of the European Society of Cardiology. Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany. Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range. The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin. Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained. The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm. Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said. ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J 2014;35[47]:3346–55), involving rivaroxaban (Xarelto). Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials. “It’s a rather unusual situation for such large numbers of patients,” said Dr. Cappato of Humanitas Research Institute in Milan.“These data go very clearly in the same direction. I think a good take-home message is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he said. The ENSURE-AF results were published online Aug. 30 in The Lancet [http://dx.doi.org/10.1016/S0140-6736(16)31474-X]. Bruce Jancin is with the Denver bureau of Frontline Medical News. The results of the ENSURE-AF trial are not likely to change any of the current indications for edoxaban use, but they demonstrated the drug is as safe and effective as enoxaparin-warfarin for anticoagulation. Edoxaban achieves therapeutic levels within 1 to 2 hours following oral administration and requires minimal laboratory monitoring (kidney function and patient weight). The tablet should not be crushed or chewed and should be swallowed whole, which may be problematic for some LTC patients. The limited need for laboratory tests and achieving rapid therapeutic efficacy for edoxaban may be of interest to geriatric cardiologists treating patients with non-valvular atrial fibrillation, but additional studies are necessary to make any conclusions about its use in patients undergoing electrical cardioversion. —Jeanne Manzi, PharmD Clinical Advisor, CVS/Caremark Rockville Centre, NY